Association of IgG N-Glycans With Adverse Outcomes in CKD

IgG N-glycosylation modulates inflammation and may influence chronic kidney disease (CKD). We investigated associations between IgG N-glycan patterns, kidney function, mortality, and kidney failure (KF) within the German CKD (GCKD) study.

IgG N-glycan peaks were measured using ultrahigh-performance liquid chromatography in 4782 GCKD participants (estimated glomerular filtration rate [eGFR]: 30-60 ml/min per 1.73 m² or overt albuminuria). We assessed associations with baseline kidney function, 6.5-year mortality, and KF using linear and Cox regression. We used bidirectional Mendelian randomization (MR) to explore causal relationships.

The cohort comprised 4782 participants (mean age: 60 years, 40% women) with a median eGFR of 46 ml/min per 1.73 m², and autoimmune kidney disease in 22%. Higher agalactosylated IgG was associated with lower eGFR (-4%/SD; 97.9% confidence interval [CI]: -6% to -3%) and higher mortality (hazard ratio [HR]: 1.39; 97.9% CI: 1.19-1.62). Conversely, higher digalactosylated and sialylated IgG were associated with higher eGFR (+5%) and lower mortality (HR: 0.68 and 0.80, respectively). Associations with urinary albumin-to-creatine ratio [UACR] and KF varied by age, sex, and autoimmune status. Core fucosylation and bisecting N-acetylglucosamine (GlcNAc) showed weaker associations, primarily with UACR. MR suggested bidirectional causal relationships between eGFR and specific N-glycan traits.

IgG N-glycan patterns reflect inflammatory aging and associate with kidney function, mortality, and KF in CKD. These findings identify IgG N-glycans as potential immunologic biomarkers for CKD. Further validation is required to confirm causal relevance.